Deciphering the intricate linkage between the gut microbiota and Alzheimer's disease: Elucidating mechanistic pathways promising therapeutic strategies

Abstract Background The gut microbiome is composed of various microorganisms such as bacteria, fungi, and protozoa, and constitutes an important part of the human gut. Its composition is closely related to human health and disease. Alzheimer's disease (AD) is a neurodegenerative disease whose underlying mechanism has not been fully elucidated. Recent research has shown that there are significant differences in the gut microbiota between AD patients and healthy individuals. Changes in the composition of gut microbiota may lead to the development of harmful factors associated with AD. In addition, the gut microbiota may play a role in the development and progression of AD through the gut–brain axis. However, the exact nature of this relationship has not been fully understood. Aims This review will elucidate the types and functions of gut microbiota and their relationship with AD and explore in depth the potential mechanisms of gut microbiota in the occurrence of AD and the prospects for treatment strategies. Methods Reviewed literature from PubMed and Web of Science using key terminologies related to AD and the gut microbiome. Results Research indicates that the gut microbiota can directly or indirectly influence the occurrence and progression of AD through metabolites, endotoxins, and the vagus nerve. Discussion This review discusses the future challenges and research directions regarding the gut microbiota in AD. Conclusion While many unresolved issues remain regarding the gut microbiota and AD, the feasibility and immense potential of treating AD by modulating the gut microbiota are evident.


| INTRODUC TI ON
The gut microbiota constitutes a complex and diverse microbial consortium within the human alimentary canal, numbering approximately 10 14 , encompassing bacteria, fungi, viruses, archaea, and protozoa.Its abundance and diversity are subject to the modulation by various factors. 1 The intestinal microbiota plays a pivotal role in training the immune system, facilitating food digestion, regulating endocrine and neural signal transduction, pharmaceutical metabolism, detoxification, among other significant functions. 2zheimer's disease (AD), as the most prevalent neurodegenerative disorder among the global elderly population, manifests neuropathological features encompassing tau protein entanglements, β-amyloid (Aβ) plaques, as well as the loss and impairment of neurons and synapses.Individuals afflicted with AD commonly exhibit apathy and depression, concomitant with impairments in communication, judgment, and cognition. 3Epidemiological reports over the past two decades delineate a marked upward trajectory in the incidence, prevalence, and mortality rates of AD, affecting millions worldwide. 4,5In recent years, heightened attention has been directed toward the role of the gut microbiota in AD.Imbalances in the gut microbiota have been implicated in central nervous system (CNS) aberrations. 6The gut microbiota, through the gut-brain axis, exerts influence on the brain involving immune, metabolic, endocrine, and neural modalities. 7Although pivotal in the pathogenesis of AD, the intricate mechanisms underlying the involvement of the gut microbiota remain elusive.The composition of the gut microbiota emerges as a potential therapeutic target for addressing inflammation and metabolic dysregulation.This review aims to elucidate the interplay between the gut microbiota and AD, explore its potential utility as a novel diagnostic tool, and investigate the feasibility of various intervention measures as adjunctive therapeutic strategies to alleviate disease progression.

| CL A SS IFI C ATI ON AND FUN C TI ON S OF THE G UT MI CROB I OTA
The gut microbiota is a complex and dynamic ecosystem housing numerous microorganisms, with colonic bacteria being the most abundant and diverse.8][19] Firmicutes and Bacteroidetes together make up about 90% of the gut microbiota (Table 1).The ecological roles, functional contributions, and interplay among these bacterial phyla remain under investigation, constituting a vibrant realm of ongoing scholarly inquiry.
The intestinal microbiota, with its intricate mechanisms, profoundly shapes human physiological processes, delving into realms such as immunity, metabolism, and the nervous system, thereby holding paramount significance in the evolution of health and disease.[22][23] Moreover, metabolic byproducts produced by the intestinal microbiota, such as purines, tryptophan, and lipids, exert expansive effects on human physiological functions. 20,24Tryptophan metabolism, via the kynurenine pathway, gives rise to downstream TA B L E 1 Taxonomy and functions of the gut microbiota.

Bifidobacterium
Acidifying the intestinal environment inhibits the proliferation of putrefactive and pathogenic bacteria, fosters the production of vitamins and amino acids, stimulates immune responses, mitigates inflammatory reactions, and safeguards the intestinal barrier, thereby reducing the translocation of endotoxins into the bloodstream 14-16  products that control biological processes such as neural transmission, inflammation, and immune responses. 25,26The intimate connection between the intestinal microbiota and lipid metabolism intertwines and reciprocally influences each other. 27The composition and abundance of lipids not only impact the microbiota but also, in turn, the microbiota, through the production of shortchain fatty acids and metabolites like trimethylamine, partake in bile acid metabolism, significantly influencing host lipid metabolic pathways. 28,29These interactions notably affect lipid levels in the blood and tissues, closely correlating with the onset of metabolic diseases. 30Finally, the intestinal microbiota, by regulating metabolites associated with Proteobacteria, such as taurine, histamine, and spermine, harmonizes the regulation of inflammasomes, profoundly influencing the host's susceptibility to diseases. 31,32

| AL ZHEIMER ' S D IS E A S E
Currently, a comprehensive consensus prevails concerning the pathogenic mechanisms underpinning AD, encompassing myriad pivotal facets. 3Chief among these considerations is the amyloid cascade hypothesis, postulating that the anomalous aggregation of Aβ assumes a central role in the pathological progression. 33,34bsequently, the prominence of inflammatory responses in the onset of AD is acknowledged, wherein instigated inflammatory processes may evoke neuronal damage. 35,36Furthermore, factors spanning glucose metabolism aberrations, compromise of the BBB, anomalies in tau protein, disturbances in autophagic-lysosomal pathways, mitochondrial functionality, cholinergic transmission, oxidative stress, and genetic susceptibility, among others, are posited to exert influence upon the progression of AD. 3 Recent inquiries suggest that dysbiosis within the gastrointestinal microbiota may emerge as a pivotal factor in the pathogenesis of AD, impacting the deposition of Aβ and the occurrence of neuroinflammation. 37These myriad factors intricately intertwine, collectively propelling the progression of AD.

| THE G UT MI CROB I OTA AND AD
The gut-brain axis is a complex signaling pathway that establishes bidirectional communication between the gastrointestinal tract and the CNS, allowing for the integration of peripheral mechanisms with cognitive centers in the brain. 38The gut microbiota, through both direct and indirect chemical signaling pathways, plays a pivotal role in regulating neuronal plasticity, epigenetics, gene expression, as well as the synthesis and release of neurotransmitters.Furthermore, the microbial byproducts released by the gut microbiota critically modulate signaling pathways associated with the regulation of proinflammatory cytokine production.These pathways, encompassing metabolism, endocrine, neural, and immune pathways, act independently or synergistically, intricately intertwined with the pathogenesis of AD (Figure 1, Table 2).

| Intestinal microbiota alterations in AD
The present inquiry elucidates significant modifications in the gut microbiota of individuals afflicted with AD and their corresponding animal models. 6The findings signify an augmentation in specific microbial phyla within the gastrointestinal microbiota of AD patients, a phenomenon concurrent with amyloid deposition in the cerebral cortex of cognitively impaired individuals. 39,40Bacterial composition in the fecal matter of AD patients demonstrates a positive correlation with amyloid levels, a decrease in lactobacilli, and an increase in lipopolysaccharides (LPS) and Escherichia coli. 41,424][45][46] These investigations elucidate the intricate alterations in the gut microbiota during the pathogenesis of AD.

| The gut microbiota and metabolism
The microbiota's metabolism may regulate neurotransmitter or their precursor biosynthesis, thereby influencing the gut-brain axis of the microbiota via neuroendocrine pathways.
The tryptophan-related metabolites orchestrated by the gut microbiota may exert a discernible influence on AD.Markedly diminished levels of indole and tryptophan (Trp) were ascertained in the plasma and erythrocytes of AD patients, in comparison to the control group. 47,48Tryptophan derivatives, secreted by the gut microbiota, intricately modulate astrocytes and microglia through the aryl hydrocarbon receptor (AhR) signaling pathway. 49Recent investigations have unveiled that indole metabolites extracted from the gut microbiota upregulate AhR, suppress the activation of the NF-κB pathway, alleviate the formation of NLRP3 inflammasomes, thereby diminishing the release of inflammatory cytokines, ultimately mitigating neuroinflammation in APP/PS1 mice. 50nsequently, the modulation of astrocyte activation, potentially alleviating central nervous system inflammation, may be facilitated by the supplementation of indole or Trp metabolites, such as those generated by bacterial tryptophanases. 515-hydroxytryptamine (5-HT), a pivotal neurotransmitter, undergoes regulation in its metabolism through the modulation of tryptophan hydroxylase in neurons and intestinal mucosal cells. 52,53The impact of 5-HT extends to monocytes and macrophages, thereby orchestrating inflammatory responses.This immunomodulation may be interconnected with neuroinflammation. 546][57] Simultaneously, it regulates the release of inflammatory cytokines such as TNFα, IFNγ, IL-1β, IL-17, and IL-6, 58 ultimately influencing neuroinflammation.Additionally, the gut microbiota, including Bifidobacteria and Lactobacilli, metabolize glutamate to produce γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the CNS. 593][64] These D-AAs, disseminated via the bloodstream, subsequently modulate the neurotransmitter system within the cerebral milieu. 65,668][69] These modifications may manifest disparately across sundry stages of AD.The gut microbiome also plays a crucial role in the metabolism and bioconversion of bile acids (BA).Experimental and clinical data have shown that there are disruptions in BA signaling in AD brain samples compared to cognitively normal individuals, as well as decreased concentrations of BA and abnormal cholesterol metabolism in serum, suggesting that the microbiome may impact AD through its effect on BA. [80][81][82][83] BA abnormalities may also increase BBB permeability when rats undergo bile duct ligation or receive injections of deoxycholic acid. 84Interestingly, endogenous hydrophilic BA Tauroursodeoxycholic acid (TUDCA) was found to reduce brain Aβ levels by regulating lipid metabolism after feeding AD mice a diet containing TUDCA for six months. 85e synthesis of trimethylamine N-oxide (TMAO) by the intestinal microbiota exhibits an inverse correlation with cognitive function in the elderly. 86Possessing the capacity to traverse the BBB, TMAO augments the activation of microglial cells and the release of inflammatory mediators. 87Investigations involving the administration of exogenous TMAO to SAMR1 and SAMP8 mice reveal its potential to induce senescence in the CA3 region neurons of the hippocampus. 88Furthermore, TMAO, by inhibiting the mTOR signaling pathway, exacerbates synaptic damage, diminishes the expression levels of proteins associated with synaptic plasticity, thereby compromising mitochondrial integrity. 88These findings underscore the pivotal role TMAO may play in the induction of AD.
SCFAs constitute metabolic byproducts emanating from the microbial metabolism of dietary fiber within the gastrointestinal milieu.
Their functional purview transcends the mere modulation of the enteric nervous system. 89Monocarboxylic acid transporters on endothelial cells enable the passage of SCFAs across the BBB. 90In the genesis and progression of AD, SCFAs exert a pivotal regulatory influence, impacting the functionality of microglial cells and thereby modulating the course of AD.Investigations reveal that, through interaction with the GPR43 receptor, SCFAs can ameliorate deficiencies in both form and function within the microglial cells of germ-free murine brains. 43 vitro experiments demonstrate the capability of SCFAs to attenuate the activity of histone deacetylases and nuclear translocation of NF-κB, thereby directly regulating and significantly diminishing LPSinduced microglia activation while modulating neuroinflammatory responses. 91Furthermore, SCFAs can influence the BBB.Colonizing germ-free mice with butyrate-producing Clostridium or propionateproducing Bacteroides, as well as administering oral sodium butyrate, reduces BBB permeability and increases occludin protein expression in the frontal cortex and hypothalamus. 92,93Intraperitoneal injection of sodium butyrate improved neurological functional deficits and restored BBB permeability in a brain injury rat model. 94Further investigation is warranted to ascertain whether SCFAs exert analogous effects on other cells within the cerebral milieu.

| The gut microbiota and endotoxins
The gut microbiota may modulate signaling pathways through the generation of LPS, amyloid-like proteins, and related signaling molecules, thereby influencing the pathogenesis of AD.The presence of bacterial-derived LPS in the brains of AD patients has been substantiated. 95Various factors, including aging, vascular defects, and diseases, contribute to the disruption of the BBB.Additionally, dysbiosis of the intestinal microbiota, leading to the abnormal production of bacterial-derived LPS and amyloid-like proteins, compromises the integrity of the intestinal barrier.This disruption amplifies the levels of cytokines associated with AD, facilitating the "leaky" of neurotoxic molecules to the cerebrovascular system. 96nsequently, this cascade triggers neuroinflammation and neuronal damage. 97Moreover, this inflammatory response may precipitate structural remodeling of the BBB and heightened permeability, ultimately fostering the genesis of AD.The entire cascade involves an augmentation in reactive oxygen species levels, initiation of the NF-κB signaling pathway, upregulation of miRNA-34a, downregulation of TREM2, and compromise of microglial phagocytic function, collectively propelling the accumulation of Aβ.100][101][102] Serum amyloid A (SAA) is a significant acute-phase protein associated with gut microbial ecology and inflammation. 103 Furthermore, SAA can affect AD by activating microglia and astrocytes via the PI3K pathway. 106SAA also affects cholesterol metabolism, which plays a vital role in brain-derived trophic factors. 107ditionally, the gut microbiota can directly stimulate Th17 cells, thereby triggering inflammation. 108

| The gut microbiota and vagus nerve
The intestinal microbiota serves as a pivotal nexus between the microbial community of the gastrointestinal tract and AD through various anatomical pathways, including the vagus nerve (VN), the spinal cord and the hypothalamus-pituitary-adrenal axis of the neuroendocrine system. 109e VN consists of mainly afferent (80%) and efferent (20%) fibers, assumes a pivotal role in the transmission of signals between the brain and the intestinal tract. 109The VN is the primary route for gut microbes to influence the brain, affecting metabolic and feeding behaviors, as well as inflammatory responses that link the brain, the gut, and other organs. 110Enteroendocrine cells containing glucose-dependent insulinotropic peptide, glucagon-like peptide-1, and peptide YY can directly communicate with VN afferent fibers, which transmit information to the central autonomic network for analysis and integration, including the paraventricular nucleus, locus coeruleus, hypothalamus, and limbic system, such as the thalamus, amygdala, and hippocampus. 109,111Studies indicate that chronic VN stimulation in AD rats alters glutamate receptor levels, thereby ameliorating memory. 112Additionally, VN stimulation activates the locus coeruleus, resulting in the release of catecholamines in the hippocampus and neocortex, which enhances synaptic plasticity and reduces inflammatory signals. 113The VN also serves as a direct conduit for signals from certain bacteria, such as Paenalcaligenes hominis, to enter the brain. 114Additionally, VN efferent fibers can synthesize and release acetylcholine, influencing not only cholinergic neurons but also exerting anti-inflammatory effects by binding to α-7 nicotinic acetylcholine receptors in macrophages, thereby inhibiting TNFα secretion. 115The interplay of the VN in the triad of the gut microbiota, behavior, and neurodegenerative diseases is intricate.However, clinical evidence conclusively proving its role in neurofunction demands further profound investigation.

| AD TRE ATMENT S TR ATEG IE S FOR THE MICROB IOTA
Given the association between the gut microbiota and AD, therapeutic interventions targeting the composition of the gut microbiota, encompassing dietary adjustments, probiotics, antibiotics, and pharmacological treatments, hold the potential to alleviate and treat AD through various avenues (Table 3).

| Diet
By influencing the types and abundance of gut bacteria, specific foods and dietary patterns can sustain host equilibrium.Research conducted on clinical trials and animal models has indicated that ketogenic diets that are high in fat and low in carbohydrates can offer symptomatic relief and improve the course of "AD". 116The ketogenic diet can selectively diminish the population of Bifidobacterium in the gut and reduce pro-inflammatory Th17 cells. 117Similarly, high adherence to the Mediterranean diet has been shown to reduce the risk of AD by 41%. 118This effect may be attributed to the propensity of the Mediterranean diet to enhance the abundance of bacteria diminished in AD while concurrently diminishing the prevalence of bacteria heightened in AD.Furthermore, alternative dietary patterns such as high-fermentable foods, 119 dietary fiber, 120 and Dietaryinulin 121 have also been discovered to confer beneficial effects on AD.Nevertheless, further research is required to ascertain how diets and their components impact the microbiota-gut-brain axis and whether the effects of diets on the microbiota translate to changes in overall brain function.

| Probiotics
Probiotics, recognized as a category of active microorganisms capable of endowing the host with health benefits, have garnered considerable attention.3][124] Investigations reveal that the administration of BGN4 and BORI probiotics among the elderly elevates serum levels of neurotrophic factors. 125Treatment of earlystage AD mice with the probiotic preparation SLB51 demonstrates not only an influence on intestinal microbial communities and plasma concentrations of metabolites but also a reduction in Aβ aggregation and the restoration of certain impaired neural protein autophagy pathways. 126Furthermore, it is highlighted that the Bifidobacterium A1 strain has the capacity to inhibit hippocampal inflammation and the expression of genes associated with immune responses in AD mice. 127Despite the current supportive evidence for the potential therapeutic role of probiotics, the development of an efficacious and safe probiotic formulation for the prevention or treatment of AD necessitates further profound inquiry.

| Pharmacological strategies
In recent times, there has been research on pharmacogenomics and the gut microbiome, which has provided a platform for de- pathway in the cerebral and colonic tissues. 133Consequently, PA efficaciously diminishes amyloid-beta levels, impedes the aggregation of amyloid-beta plaques, retards neuroinflammation within the cerebral regions of AD-afflicted mice, and mitigates the hyperphosphorylation at various tau protein sites. 37,133Scutellaria baicalensis root, 134 Morinda officinali 135,136 and Cyanidin-3-O-glucoside 137 exhibit analogous regulatory mechanisms.Moreover, a multitude of empirical investigations have substantiated the extraordinary effectiveness of TCM formulations in addressing the intricacies of AD. 138,139 These formulations, through the modulation of the intricate ecosystem of the gastrointestinal microbiota, evince efficacy for therapeutic interventions in AD.For instance, Huanglian-Jiedu Decoction augments SCFAs levels, mitigates central and peripheral lipid metabolism disorders and inflammation, diminishes amyloid-beta deposition, and augments cognitive function. 140Furthermore, TCM formulations such as Liuwei-Dihuang Decoction, 141,142 Chaihu-Shugan-San, 143 Jia-Jian-Di-Huang-Yin-Zi Decoction 144 efficacy in modulating the gastrointestinal microbiota to ameliorate the therapeutic outcomes of AD.Although other natural compounds with potential therapeutic benefits and minimal side effects may exist, they remain undiscovered or unidentified.

| Fecal microbiota transplantation
Fecal microbiota transplantation (FMT) is a technique that transfers gut microbiota from a healthy donor to a recipient with a disturbed gut microbiota, aiming to restore the ecological balance. 145

| CON CLUS I ON S AND FUTURE PER S PEC TIVE S
The correlation betwixt the enteric microbiota and AD has surfaced as a novel perspective in the amelioration of this affliction.O'er the bygone two decades, considerable advancement hath been attained, elucidating the potential of the enteric microbiota as a target for AD therapy.Despite these strides, there is a requisite to elucidate the causative relationship betwixt the enteric microbiota and AD to formulate efficacious and safe therapeutic interventions.
In adjunct to the enteric microbiota, the oral microbiota also exerts a potential sway on the pathogenic mechanisms of AD.
Alterations in the oral microbiota impact the pathogenesis of AD through sundry mechanisms, including the initiation or exacerbation of neuroinflammation via hematogenous dissemination. 148The oral microbiota communicates with the enteric microbiota through the oral-gut-brain axis, and the imbalance in the oral microbiota may disrupt the equilibrium of the enteric microbiota, thereby exacerbating the pathophysiology of AD.A more profound exploration of the interplay betwixt the oral microbiota and AD will contribute to the exploration of novel therapeutic and preventive approaches.
Understanding molecular interactions and the potential to ameliorate the condition of AD patients by modulating the oral microbiota is of paramount importance.
In pondering the prospective alleviation of AD susceptibility through microbial therapy, due regard must be accorded to its ef- 70,71 D-AAs may exert an impact on AD through various mechanisms.D-serine has the capacity to attenuate neuronal demise, forestall cellular apoptosis,72 stimulate neural stem cell proliferation, and neuronal differentiation,73 modulate the activity of N-methyl-D-aspartate receptors, thereby influencing synaptic plasticity and neurodevelopment.74,75Furthermore, D-serine, by inhibiting the JNK signaling pathway, ameliorates cognitive impairment induced by hippocampal Aβ42 injection.76Investigations also indicate that dietary or aqueous supplementation of L-Serine or D-Serine alleviates memory deficits associated with reduced D-Serine levels and plasticity defects in 3xTg-AD mice.77Additionally, the diminished levels of D-Glutamate in AD warrant further exploration of its neurophysiological implications.78,79Future research should delve into exploring the impact of D-AAs in the gut microbiota on host health and disease, particularly regarding the specific mechanistic roles of D-AAs in AD.F I G U R E 1 Communication between the gut microbiome and brain.A pictorial representation elucidating the manifold established bidirectional conduits of communication within the gastrointestinal-neuronal axis in relation to the gut microbiota associated with AD, encompassing: (1) pathways of immune modulation, (2) transmission of signals pertaining to gut endocrine secretions and microbial metabolites, and (3) the neural pathway of the VN.BA, bile acids; D-AAs, D-amino acids; EEC, enteroendocrine cell; LPS, lipopolysaccharide; SAA, serum amyloid A; SCFAs, short-chain fatty acids; TMAO, trimethylamine-N-oxide; Trp, tryptophan; VN, vagus nerve.
It has been locally detected in the brains of AD patients and co-localized with senile plaques.SAA can influence AD by promoting Th17 cellmediated neuroinflammation, regulating cholesterol metabolism, and activating glial cells.Experimental evidence demonstrates that SAA can directly induce the differentiation of Th17 cells, leading to increased expression of Th17 pro-inflammatory cytokines, such as IL-17 and IL-22, within the hippocampus; these cytokines exhibit elevated concentrations in cerebrospinal fluid and serum. 104,105 novel approaches to treat AD.The modulation of gut microbiota through drug interventions may offer a promising method of treating AD.GV-971, a low-molecular-weight sodium oligo-mannuronate, can inhibit gut dysbiosis and related accumulation of phenylalanine/isoleucine in AD mouse models, controlling neuroinflammation and reversing cognitive impairment.128Furthermore, antimicrobial agents are frequently employed on an extensive scale for the elimination or prophylaxis of bacterial colonization within the human organism, as opposed to selectively targeting distinct bacterial strains.Consequently, the application of broad-spectrum antimicrobials may have repercussions on the constitution of the intestinal microbiota.Despite established findings in the AD murine model suggesting that prolonged administration of broad-spectrum antimicrobials can diminish the deposition of Aβ plaques and mitigate the localized glial cell response to these plaques, contemporary scientific evidence remains inadequate to substantiate the deployment of antimicrobials as a therapeutic modality for AD.129In AD, the impacts of antimicrobials may encompass a comprehensive and potentially paradoxical spectrum, contingent upon the nature of the antimicrobial agent and the specific roles of the microbiota in the pathogenesis of AD.130 Traditional Chinese medicine (TCM) formulations have shown advantages over other pharmacological agents, such as their complex composition, multiple target modulation, low side effects and high biocompatibility.131TCM interventions can regulate the intestinal microbiota composition and improve the gut microecology, which may benefit the CNS disorders and enhance therapeutic outcomes.132Patchouli alcohol (PA), a compound derived from the common traditional Chinese herb Pogostemonis Herba, stands as a principal bioactive constituent.Its application in murine models of AD ameliorates the ecological equilibrium of the intestinal milieu, concurrently repressing the activation of the C/EBPβ/AEP signaling ficacy within vulnerable cohorts.Diligent inquiries into the curative ramifications of microbiota intervention measures are imperative, encompassing synergistic impacts, considerations of sample magnitude, and investigations into the consequences of protracted interventions.Furthermore, circumspect evaluation is warranted for the repercussions of alternative microbiota-targeted therapeutic modalities on pharmacological interventions.Notwithstanding the expansive potential of gut microbiome modulation, extant strategies for regulating the gut microbiota in the context of AD remain inadequately refined.A more encompassing research undertaking is requisite to ascertain optimal intervention methodologies and their enduring ramifications, thereby providing viable and secure pathways for the prevention and management of AD.Such endeavors will contribute to elucidating underlying mechanisms, advancing deeper theoretical frameworks for interventions involving the regulation of the gut microbiota or the utilization of bioactive constituents.
Involvement of the gut microbiota in regulating AD pathology.
Therapeutic intervention of AD through gut microbiota manipulation.
TA B L E 3 147 has been explored as a potential therapy for neurological disorders.Sun et al. showed that FMT from WT donors improved cognitive function and reduced Aβ plaque load and soluble Aβ40 and Aβ42 levels in APP/PS1 mice.146FMT also increased the expression of synaptic plasticity-related proteins and the levels of beneficial SCFAs, especially butyrate, in the gut.Similarly, Fujii et al. reported that WT mice receiving FMT from human donors with AD, especially at a younger age, exhibited cognitive impairments compared with those receiving FMT from healthy donors.147